Immunosuppressants may provide protection against Parkinson's disease

People taking immunosuppressants, drugs that suppress the immune system, are at lower risk of developing Parkinson's disease, according to a new study published in the Annals of Clinical and Translational Neurology.

The study was conducted by Brad A. Racette, Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, and colleagues to examine the risk of Parkinson disease in relation to use of immunosuppressants.

Parkinson's is a neurodegenerative disease that affects about 10 million people worldwide. Its causes are not well-understood. Although numerous studies have attempted to identify neuroprotective medications to slow the progression of Parkinson disease (PD), all have failed to meet primary endpoints.

For the study, the researchers analyzed Medicare Part D prescription drug data on 48,295 people diagnosed with Parkinson's in 2009 and 52,324 people never diagnosed with Parkinson's. They identified 26 commonly prescribed immunosuppressant drugs, representing six classes of medications. The researchers determined which people in the data set had been prescribed any of the drugs a year or more before the date of diagnosis or by a pre-set cutoff date. Prescriptions written in the 12 months before diagnosis or by the cutoff were excluded to rule out any chance that the prescriptions might have been linked to early signs of the disease.

They analyzed millions of medical records and developed an algorithm to predict which people would be diagnosed with the disease. As they mined the data, they discovered that people with several types of autoimmune diseases, including ulcerative colitis, were less likely to be diagnosed with Parkinson's than the general population.

The researchers found that inosine monophosphate dehydrogenase (IMDH) inhibitors and corticosteroids were both associated with a lower risk of Parkinson disease. People taking drugs in either of two classes were significantly less likely to develop Parkinson's than those taking no immunosuppressants.

The findings suggest that a person's own immune system helps nudge him or her down the path toward Parkinson's. Restraining the immune system with drugs potentially could prevent the neurological disorder, which is characterized by tremors, slow movements, stiffness, and difficulty walking.

"The idea that a person's immune system could be contributing to neurologic damage has been suggested for quite some time," said Racette. "We've found that taking certain classes of immunosuppressant drugs reduces the risk of developing Parkinson's. One group of drugs, in particular, looks really promising and warrants further investigation to determine whether it can slow disease progression."

When the researchers included specific autoimmune diseases in their analysis, the calculated risks didn't change, suggesting that the difference was due to use of the drugs, not the underlying diseases they were treating.

The findings suggest that tamping down immunity with drugs may keep Parkinson's disease at bay. But doing so also makes people more susceptible to infectious diseases and cancer. The benefits of immunosuppressive drugs outweigh the costs for people with serious autoimmune diseases like rheumatoid arthritis. But doctors probably would hesitate to prescribe risky drugs to healthy people to stave off Parkinson's, especially since there is no reliable way to predict who is on track to develop the disease.

"What we really need is a drug for people who are newly diagnosed, to prevent the disease from worsening," Racette said. "It's a reasonable assumption that if a drug reduces the risk of getting Parkinson's, it also will slow disease progression, and we're exploring that now."

Corticosteroids have many side effects, and doctors already try to minimize their use, so the focus of the researchers have now shifted to IMDH inhibitors.

"Our next step is to conduct a proof-of-concept study with people newly diagnosed with Parkinson's disease to see whether these drugs have the effect on the immune system that we'd expect," Racette said. "It's too early to be thinking about clinical trials to see whether it modifies the disease, but the potential is intriguing."

Based on the study, the authors concluded that use of corticosteroids and inosine monophosphate dehydrogenase inhibitors might lower the risk of Parkinson disease.

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